Metal radionuclides are widely used in diagnostic imaging. Radioisotopes of gallium, indium, technetium and copper are used in nuclear medicine studies while gadolinium chelates act as paramagnetic contrast agents in conjunction with nuclear magnetic resonance imaging (MRI). New improved chelating agents for these metal ions have been designed. The properties of these new chelating agents will be predicted utilizing molecular mechanic calculations, the ligands will be synthesized and the characteristics of the metal complexes studied by physicochemical methods as well as in vivo and in vitro biological evaluation. Chelates have been designed for maximum thermadynamic stability by using ligands with donor groups highly selective for the particular metals. The charge and lipophilicity of the chelates will be altered by changing the donor groups as well as the addition of alkyl groups and other substituents. The metal chelates will be functionalized with several types of linkages to allow covalent attachment to proteins and peptides. Particular emphasis is being given to new ligands for the metal indium and copper. The stability constants of the new ligands will be determined and the kinetics of metal dissociation measured. The biological behavior of both the ligands and bifunctional chelates attached to proteins and peptides will be determined in vitro and in animal models. The synthesis characterization and physicochemical studies will be carried out at Texas A&M University while the in vitro and in vivo evaluation of the pharmaceutical preparations will be undertaken at Washington University.